Bacteriophages in the microbiome are the focus of a new project at the Quadram Institute that will uncover how they interact with the gut to influence health.
Dr Evelien Adriaenssens has received funding from the Biotechnology and Biological Sciences Research Council (BBSRC) to study how these viruses that infect bacteria contribute to a healthy gut microbiome.
In collaboration with Professor Nathalie Juge and Professor Lindsay Hall, the research team will unpick how the communities of billions of bacteriophage particles that are naturally resident in the gut interact with the cells of the gut lining, and what implications this has for health. This knowledge will also support the development of phage-based therapies.
The gut microbiome is a complex community of microbes that colonises the digestive system. It helps prevent disease-causing bacteria from infecting us, and also has a major role in maintaining optimum health by breaking down food and releasing metabolites that benefit the cells of gut lining, or epithelium.
Alterations in the composition of the microbiome, and the profile of these metabolites, have been associated with a number of conditions, not just in the gut itself but also in the immune system and other organs, including the liver and brain.
This has driven a large body of research into the microbiome’s influence on health, but most of this has focused on the bacteria. Less has focused on the bacteriophages that infect these bacteria, in part because they are harder to identify and work with.
However, advances in technology have delivered high-throughput genome sequencing techniques that have shown that a healthy gut microbiome hosts hundreds of different phage species.
Transmission electron micrography of bacteriophages (blue). Image by Adriaenssens Group, Quadram Institute Bioscience
What is this profusion of bacteriophages in the microbiome doing?
This is the question the research team will address by combining their complementary expertise.
Dr Adriaenssens and Dr Teagan Brown are microbiologists who have specialised in the study of bacteriophages. Prof. Juge and Dr Tanja Šuligoj are experts in the gut lining and its interactions with microbes and have established within the Quadram Institute a human biopsy-derived intestinal organoid-based cell model system that accurately mimics conditions in the gut lining. Prof. Hall and her team focus on understanding how establishing a healthy microbiome benefits health, through long-term clinical studies. Dr Andrea Telatin is a bioinformatics researcher who develops computational tools for analysing microbiome data.
Together, their aim will be to fill in the gaps in our knowledge of the bacteriophage community in the gut microbiome. They will identify the phages that have adapted specifically to the gut and to the epithelium, and how the epithelial cells respond, building a complete picture of the interactions that underpin a stable, healthy microbiome.
The new project will also support the potential use of bacteriophages as therapeutic agents. Because they only infect bacterial cells, phages have shown promise as replacements for antibiotics. They tend to be more specific, targeting a much narrower range of bacteria than traditional broad spectrum antibiotics. With antimicrobial resistance on the rise, phage therapy could provide a new weapon against resistant bacteria, but we need to know more about how phages interact with the gut lining, and the immune system, to ensure they can deployed safely and effectively.
“Bacteriophages are fascinating organisms that are abundant in our microbiome. They are promising alternatives to antibiotics but we need to know more about how they interact with our gut itself, so we can make informed choices about suitability of specific phages for therapy” said Dr Adriaenssens.
“The funding provided by BBSRC for this project allows me to team up with Prof Nathalie Juge and Prof Lindsay Hall to combine all the strengths of the Quadram Institute to investigate improving gut health across life.”
“We’re excited to exploit our human intestinal models to find out more about how phages may modulate gut barrier function” said Prof. Juge. “We are very much looking forward to this new collaboration with phage experts.”